Abstract
The nuclear pore complex, composed of proteins termed nucleoporins (Nups), is responsible for nucleocytoplasmic transport in eukaryotes. Nuclear pore complexes (NPCs) form an annular structure composed of the nuclear ring, cytoplasmic ring, a membrane ring, and two inner rings. Nup192 is a major component of the NPC’s inner ring. We report the crystal structure of Saccharomyces cerevisiae Nup192 residues 2–960 [ScNup192(2–960)], which adopts an α-helical fold with three domains (i.e., D1, D2, and D3). Small angle X-ray scattering and electron microscopy (EM) studies reveal that ScNup192(2–960) could undergo long-range transition between “open” and “closed” conformations. We obtained a structural model of full-length ScNup192 based on EM, the structure of ScNup192(2–960), and homology modeling. Evolutionary analyses using the ScNup192(2–960) structure suggest that NPCs and vesicle-coating complexes are descended from a common membrane-coating ancestral complex. We show that suppression of Nup192 expression leads to compromised nuclear transport and hypothesize a role for Nup192 in modulating the permeability of the NPC central channel.
► Structure of the N-terminal half of the yeast Nup192, a major component in the NPC ► Structural insights in to the conformational dynamics of ScNup192 by SAXS and EM ► Nup192 appears structurally related to karyopherins and vesicle coating proteins ► Functional data suggests that the Nup192 is necessary for efficient nuclear transport
Sampathkumar et al. describe the crystal structure of the N-terminal half of S. cerevisiae Nup192, a major component of the nuclear pore complex (NPC), and an electron microscopy model of the full-length protein. Nup192 is flexible, structurally related to karyopherins, and may help modulate the NPC permeability.